Intimal Hyperplasia (IH) is a leading cause of delayed graft failure in vascular surgery. Recently, an intracellular protein dawn as the proteasome has been shown to be centrally important in regulating growth, cell cycle control, transcription, and intracellular signal transduction in many types of eukaryotic cells. Its function in vascular smooth muscle cells (VSMC) and III has not been defined. The goal of this project is to define the function and regulation of the proteasome in human VSMC in vitro. The presence of the proteasome and its activators will be identified in vascular sections using immunohistochemistry. proliferation and migration of VSMC in response to proteasome inhibition and differential activation will be assessed. Finally, the role of the proteasome in intracellular signal transduction of known vascular mitogens will be assayed. The success of this project will provide evidence identifying the proteasome as an important mediator of vascular smooth muscle cell homeostasis and intimal hyperplasia. Furthermore, our understanding of the intracellular events in vascular smooth muscle cells leading to intimal hyperplasia will be greatly improved.